DESCRIPTION (provided by principal investigator): The insulin-like growth factor (IGF) system is highly conserved across species and plays a critical role in all phases of the mammalian life cycle, from fetal development through childhood / pubertal growth and adulthood. Insulin-like growth factor-1 (IGF-I), an important peptide hormone of the IGF system, is involved in regulation cell cycle - promoting cell proliferation and somatic growth while inhibiting apoptosis - in tissues throughout the body. In humans, the role of the IGF system in aging and age-related diseases is still poorly understood, though this field of research has raised hopes for new drugs that slow the aging process by modulating IGF pathways. The present study will assess the association of circulating levels of IGF-I, IGF-I, and IGF binding proteins (IGFBP-1, IGFBP-2, IGFBP-3) with functional limitation, disability, performance-based tests of physical function, brain morphologic changes, and survival/longevity among older adults. The study will use specimens and data from the Cardiovascular Health Study (CHS) cohort - a large multi-center NIH-funded cohort of n=5,888 community-dwelling men and women 65 years or older, with detailed longitudinal data capturing age-related outcomes. Follow-up in CHS is now over 15 years, which will allow us to go beyond any prior studies by defining within-individual trajectories of IGF-I and IGFBP levels from repeated blood samples, and relating these measurements to age-related outcomes. Further studies will identify genetic determinants of IGF-I and IGFBPs using a whole-genome approach, with replication in the Framingham and Rotterdam cohorts. PUBLIC HEALTH RELEVANCE: The insulin-like growth factor (IGF) system appears to play a major role in the aging process. However, in humans, the role of the IGF system in aging and age-related diseases is still poorly understood. This project will assess the relationship of the IGF system with disability, changes in brain structure, and longevity among 65+ year old men and women, with the long-term goal of informing the development of new drugs that slow the aging process by modulating IGF pathways.